Antigen heterogeneity within human tumor cell populations can be attributed somewhat to the intrinsic ability of the cells to modulate the level of expression of certain tumor antigens by: 1) cell cycle kinetics 2) clonal variability and 3) cell-to-cell communication in three-dimensional organoids. Studies wee carried out to establish that exogenously administered biological response modifiers, such as the recombinant human interferons, can override the intrinsic modulation of these antigens resulting in an increase in the percent of the cell population expressing the monoclonal-antibody (MAb) defined tumor antigen as well as increasing the amount of antigen expressed per cell. Utilizing eight different human breast tumor cell lines, it was shown that both recombinant human leukocyte (alpha) and gamma (type I and II) interferons were effective in augmenting several MAb-defined cell surface tumor antigens. In addition, alpha interferon was shown to increase the expression of TAG-72 on human breast tumor cells isolated from a patient's pleural effusion. Additional studies demonstrated that the in vivo administration of recombinant leukocyte (clone A) interferon was effective in increasing the amount of tumor antigen expressed by a human colon xenograft in situ and also augmented the localization of a radiolabeled MAb to the tumor site. Thus, these studies may lead to the new strategies designed to use recombinant interferon as an adjunct for MAb-binding to human carcinoma cell population.